Liraglutide Attenuates Disease Severity in Experimental Autoimmune Encephalomyelitis by Modulating Splenic T Helper Cell Subsets.
Shuang Song, Bin Li, Ruoyi Guo, Yi Zhou, Yumei Xue, Li Guo
Abstract
Open AccessOBJECTIVE: To investigate the therapeutic effects of liraglutide, a glucagon-like peptide-1 receptor agonist, on clinical progression and splenic T-cell subsets in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. METHODS: EAE was induced in C57BL/6 mice via myelin oligodendrocyte glycoprotein immunization. The mice were divided into three groups: healthy controls (n = 8), EAE (n = 10), and EAE + liraglutide (n = 10). The EAE + liraglutide treatment group received subcutaneous liraglutide (10 µg/kg every other day) starting at 8 days postimmunization. Body weight and disease score were monitored for 30 days, and part of the animals (n = 4 for each group) were sacrificed 20 days postimmunization for flow cytometry of splenocytes, and splenic T helper 1 (Th1) and regulatory T (Treg) cell proportions were analyzed. RESULTS: Liraglutide significantly reduced maximum clinical scores (EAE 2.50 ± 0.41 versus EAE + liraglutide 1.75 ± 0.59, p = 0.005), but no significant differences in body weight were observed between the EAE and EAE + liraglutide groups. EAE induction decreased the proportion of splenic Treg cells (6.38% ± 0.72% versus control 10.55% ± 0.87%, p = 0.013), with liraglutide treatment showing no significant effect on Treg proportion relative to EAE alone (7.53% ± 1.54% versus 6.38% ± 0.72%, p = 0.975). However, the proportion of Th1 cells significantly increased after EAE induction (11.95% ± 1.58% versus control 6.05% ± 3.23%, p = 0.025), which was reduced by liraglutide (5.94% ± 2.53% versus EAE, p = 0.025). CONCLUSIONS: The present preliminary findings demonstrate that liraglutide alleviates EAE severity, probably through peripheral immunomodulatory effects of splenic T helper cells.